Abstract The ketogenic diet (KD) is an established non-pharmacological treatment for drug-resistant epilepsy (DRE) in children, but data from large prospective cohorts in China remain limited. We conducted a prospective observational study of children with DRE whose caregivers elected KD treatment compared with those who continued conventional therapy. Seizure frequency, EEG findings, cognitive assessments, and adverse events were monitored over six months. A total of 136 children were enrolled (73 KD; 63 controls). At six months, children receiving KD showed a higher proportion of seizure reduction ≥ 50% compared with controls. EEG evaluations revealed improvements in background activity and reduction in epileptiform discharges, and cognitive assessments demonstrated gains in specific domains. Adverse effects were generally mild and manageable with dietary adjustments. In this single-center prospective cohort, KD was associated with improved seizure control, EEG patterns, and cognitive performance over six months compared with conventional therapy. While limited by non-randomized design and short follow-up, these findings provide real-world evidence supporting KD as a feasible and safe adjunctive therapy for pediatric DRE in China. Longer randomized studies are warranted to establish causality and evaluate long-term outcomes.

OBJECTIVE:To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously. METHODS:Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-062-01). RESULTS:Child 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism, developmental delay, short stature, microcephaly, cleft palate, cryptorchidism, hypospadias, recurrent infections and immunological abnormalities. Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT (p.Y2199Ifs*65) variant of the KMT2D gene and a heterozygous c.1892G>A (p.R631Q) variant of the PIK3R1 gene. This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36. Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy, Albright's hereditary osteodystrophy, long body trunk, short limbs, hypocalcemia, hyperphosphatemia and hyperparathyroidism. The child also had a family history of short stature. Whole exome sequencing revealed that she had harbored a heterozygous c.2T>C (p.Met1?) variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene. The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature. CONCLUSION:When the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant, multiple pathogenic variants should be considered, and this may lead to the diagnosis of co-morbid genetic diseases. To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of co-morbid genetic diseases.

BACKGROUND:The ADP-ribosylation factor 1 (ARF1) gene encodes a protein which plays a critical role in intra-Golgi transport. Clinical evidence suggests that individuals harbouring variants in the ARF1 gene display a consistent set of phenotypic features, including intellectual disability, microcephaly, epilepsy, and periventricular nodular heterotopia (PVNH). METHODS:This study describes the case of a 6-year and 5-month-old female presenting with focal seizures on a fixed side that were resistant to various anti-seizure medications. The genetic aetiology was elucidated through exome sequencing of the pedigree. The pathogenicity of the identified variant was subsequently assessed using molecular dynamics structural analysis, western blotting, and co-immunoprecipitation techniques. RESULTS:A de novo variant, c.509T > C (p.Leu170Pro), was detected in the ARF1 gene, and functional analysis demonstrated that this modification is anticipated to hinder its association with the Golgi-localising, γ-adaptin ear homology domain and ARF-binding protein, thereby playing a role in the pathogenesis of the disease. CONCLUSION:This study introduces the initial instance of ARF1-related disease in China, wherein the patient is without the presence of PVNH. The findings add novel clinical phenotypes to the range of ARF1-related diseases, and an investigation into the potential pathogenic mechanisms of this condition was conducted by confirming the deleterious impacts of the variant.

Objective:To investigate the effect of visual stimulation on epilepsy susceptibility in neonatal hypoglycemic brain injury (HBIN) rats and its underlying mechanisms. Methods:Seventy-five 2-day-old Sprague-Dawley rats were divided into three groups: control (N, N = 25), model (NH, N = 25), and visual stimulation (NH-V, N = 25). The NH and NH-V groups were injected with insulin (40 U/kg) on postnatal days 2, 4, and 6, and blood glucose was monitored. The NH-V group received daily 2-h visual stimulation from P14 to P28. At P21, brain Magnetic Resonance Imaging (MRI) was performed. Pentylenetetrazol (PTZ) was injected to induce seizures and recorded at P28. Brain tissue was analyzed for Brain-Derived Neurotrophic Factor (BDNF) and Synaptophysin (SYN) expression. Results:(i) In the NH and NH-V groups, blood glucose decreased after insulin injection, with behavioral changes observed at 1-4 h. One rat in the NH group had spontaneous seizures. (ii) MRI at 15 days showed occipital lobe abnormalities in 50% of NH rats, with no changes in controls. (iii) In PTZ-induced seizures, the N group had significantly lower seizure scores than the NH group, with the NH-V group showing further reduction. (iv) BDNF and SYN expression were higher in the NH-V group compared to the NH group. Conclusion:Visual stimulation reduces epilepsy susceptibility in neonatal HBIN rats, likely through upregulation of BDNF and SYN expression in the occipital cortex.

Background Lamb-Shaffer syndrome (LAMSHF, OMIM: 616803) is a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, poor expressive speech, which is attributed to haploinsufficiency by heterozygous variants of SOX5 gene (SRY-Box Transcription Factor 5, HGNC: 11201) on chromosome 12p12. A total of 113 cases have been reported in the world, however, only 3 cases have been reported.in China. Here, we aimed to report novel variants of SOX5 gene and provide examples for clinical diagnosis by reporting the clinical phenotype of a series of Chinese patients with LAMSHF. Methods This study retrospectively collected the information of families of LAMSHF patients in China. Whole Exome Sequencing (WES) were performed to confirm the diagnosis of 4 children with unexplained developmental delay or epilepsy. A minigene splicing assay was used to verify whether the splice variant affected splicing. Meanwhile, a literature review was conducted to analyze the clinical and genetic characteristics of patients with LAMSHF. Results Three of the LAMSHF patients had a de novo heterozygous mutation in the SOX5 gene respectively, c.290delC (p.Pro97fs*30), chr12:23686019_24048958del, c.1772-1C > A, and the remaining one had a mutation inherited from his father, c.1411C > T (p.Arg471*). The main clinical manifestations of these children were presented with global developmental delays, and one of them also had seizures. And the results of the minigene experiment indicated that the splice variant, c.1772-1C > A, transcribed a novel mRNA product which leaded to the formation of a truncated protein. Conclusions Through a comprehensive review and analysis of existing literature and this study showed intellectual disability, speech delay and facial dysmorphisms were common clinical manifestation, while the seizures and EEG abnormalities were rare (21/95, 22.16%). Notably, we represent the largest sample size of LAMSHF in Asia that encompasses previously unreported SOX5 gene mutation, and a minigene testing have been conducted to validate the pathogenicity of the c.1772-1C > A splice variant. The research further expands the phenotype and genotype of LAMSHF while offers novel insights for potential pathogenicity of genes locus.

ObjectiveThis study aims to describe the characteristics of the brain network attributes in children diagnosed with Infantile Epileptic Spasms Syndrome (IESS) and to determine the influence exerted by adrenocorticotrophic hormone (ACTH) or methylprednisolone (MP) on network attributes.MethodsIn this retrospective cohort study, we recruited 19 infants diagnosed with IESS and 10 healthy subjects as the control from the Pediatric Neurology Department at the Third Affiliated Hospital of Zhengzhou University between October 2019 and December 2020. The first thirty-minute processed electroencephalograms (EEGs) were clipped and filtered into EEG frequency bands (2 s each). A comparative assessment was conducted between the IESS group and the controls as well as the pre- and post-treatment in the IESS group. Mutual information values for each EEG channel were collected and compared including characteristic path length (CPL), node degree (ND), clustering coefficient (CC), and betweenness centrality (BC), based on graph theory.ResultsComparing the control group, in the IESS group, there was an increase in CPL of the Delta band, and a decrease in ND and CC of the Delta band during the waking period, contrary to those during the sleeping period (P < 0.05), a decreased in CPL of the fast waves and an increase in ND and CC (P < 0.05) in the sleep-wake cycle, and a decrease in ND and CC of the Theta band in the waking phase. Post-treatment compared with the pre-treatment, during the waking ictal phase, there was a noted decrease in CPL in the Delta band and fast waves, while an increase was observed in ND and CC (P < 0.05).ConclusionsThe Delta band and fast waves are crucial components of the network attributes in IESS.SignificanceThis investigation provides a precise characterization of the brain network in children afflicted with IESS, and lays the groundwork for predicting the prognosis using graph theory.

Objective To analyze the clinical data of 2 cases of CHD2 gene related epilepsy and to investigate their phenotypes and gene mutation types. Methods The clinical data of 2 probands and their families were collected. The peripheral blood of the probands and their parents was extracted for genomic DNA. High-throughput sequencing was used to detect the exons and their intronic regions to define the gene mutation sites, and the pathogenic variations were verified by PCR-Sanger sequencing. The conservativeness of gene variation sites in the probands was analyzed by UCSC softwares, and the pathogenicity of variation sites was analyzed by using the Varseak and Mutation Taster softwares. Results Convulsions developed in two patients at the age of about 3 years old. Proband 1 was manifested with tonic-clonic seizures, which was controlled by levetiracetam and sodium valproate treatment after being diagnosed as epilepsy and autism spectrum disorder. This proband was detected heterozygous mutation of CHD2 gene c.2877-1＿2877delGCinsAA, which was a splicing receptor mutation. The corresponding base（C） at C.2877-1 and the corresponding amino acid（asparagine） at c.2877 were highly conserved in 13 species. Parental verification and query of human gene database indicated that it was a de novo mutation. The analysis results of Varseak predicted that the mutation would lead to changes in protein sequence and structure, and was possibly pathogenic according to the ACMG classification. Proband 2 was diagnosed with Lennox-Gastaut syndrome, with multiple seizure patterns combined with severe developmental delay. Seizures were controlled after treatment with levetiracetam, while other drugs had poor efficacy. There was a heterozygous mutation of CHD2 gene c.361C＞T（p.Arg121Ter）,which was a nonsense mutation.The 121amino acid（arginine）corresponding to the c.361C＞T mutation was highly conserved in 13species.The mutation was verified as a de novo mutation in the pedigree,Mutation Taster software analysis indicated that it was suspected to be pathogenic mutation,and it was pathogenic according to the ACMG classification.Conclusion The children with epilepsy accompanied by developmental delay and autism spectrum disorder should consider the CHD2 gene mutation,and genetic test contributes to the early diagnosis.

[This corrects the article DOI: 10.3389/fped.2022.878099.].

目的 观察癫痫患儿规范应用抗癫痫发作药物(antiseizure medications,ASMs)或联合糖皮质激素治疗后低纤维蛋白原血症发生情况及严重程度,探讨抗癫痫治疗后发生低纤维蛋白原血症的因素和治疗结局.方法 33例应用ASMs或联合糖皮质激素规范治疗后发生低纤维蛋白原血症的癫痫患儿,确诊低纤维蛋白原血症后给予人纤维蛋白原、必要时降低丙戊酸钠药物剂量等治疗.记录癫痫发作类型、综合征类型、病因、治疗后发生低纤维蛋白原血症的中位时间、发生低纤维蛋白原血症时的治疗方案;于抗癫痫治疗前、诊断低纤维蛋白原血症时、低纤维蛋白原血症治疗次日及治疗后1个月检测纤维蛋白原(fibrinogen,Fib)、凝血酶原时间、凝血酶时间、活化部分凝血活酶时间、纤维蛋白降解产物、D-二聚体、中性粒细胞计数、白细胞计数、血红蛋白、血小板计数.随访至2022年8月,观察患儿低纤维蛋白原血症复发情况.结果 33例发作类型为痉挛发作24例,强直-阵挛发作6例,强直痉挛发作2例,肌阵挛发作1例;婴儿癫痫性痉挛综合征21例;病因不明14例,结构性病因13例,遗传性病因6例;1例因不易止血发现且合并轻度肝功能损伤,余32例在随访期间常规检测血常规、凝血功能时发现.诊断低纤维蛋白原血症时,33例中32例应用丙戊酸钠,其中26例(含21例婴儿癫痫性痉挛综合征)应用糖皮质激素联合丙戊酸钠等ASMs,1例应用糖皮质激素联合左乙拉西坦、托吡酯及氯硝西泮,6例未应用糖皮质激素(5例应用丙戊酸钠联合其他ASMs,1例单用丙戊酸钠).诊断低纤维蛋白原血症时Fib水平[0.930(0.850,0.980)g/L]低于抗癫痫治疗前[2.460(2.140,2.675)g/L](Z=-5.013,P＜0.001),凝血酶时间[(20.676±1.756)s]长于抗癫痫治疗前[(18.284±1.605)s](t=7.478,P＜0.001),活化部分凝血活酶时间[(34.803±5.446)s]短于抗癫痫治疗前[(40.447±5.402)s](t=-6.030,P＜0.001).31例诊断低纤维蛋白原血症时Fib水平＜1.0 g/L,静脉滴注人纤维蛋白原,30例应用丙戊酸钠者同时口服左卡尼汀,次日低纤维蛋白原血症纠正;2例诊断低纤维蛋白原血症时Fib水平为1.0 g/L,口服左卡尼汀并降低丙戊酸钠剂量后低纤维蛋白原血症得到纠正.33例低纤维蛋白原血症治疗次日Fib水平[1.950(1.515,2.490)g/L]高于诊断低纤维蛋白原血症时(P＜0.05),凝血酶原时间[(12.564±1.140)s]、凝血酶时间[(17.491±1.515)s]均短于诊断低纤维蛋白原血症时[(13.752±1.591)、(20.676±1.756)s](P＜0.05);低纤维蛋白原血症治疗1个月Fib水平[1.550(1.390,1.659)g/L]高于诊断低纤维蛋白原血症时(P＜0.05),凝血酶时间[(17.680±1.465)s]短于诊断低纤维蛋白原血症时(P＜0.05),活化部分凝血活酶时间[(37.601±5.728)s]长于诊断低纤维蛋白原血症时(P＜0.05).中位随访32.75(24.90,43.88)个月,1例间隔2个月再次发生低纤维蛋白原血症,再次静脉滴注人纤维蛋白原并降低丙戊酸钠剂量后纠正,余患儿未再发生低纤维蛋白原血症.结论 应用丙戊酸钠或联合糖皮质激素治疗、发作类型为婴儿癫痫性痉挛综合征的癫痫患儿易发生低纤维蛋白原血症,临床应注意监测癫痫患儿凝血功能,发现低纤维蛋白原血症后及时处理,减少相关出血并发症.

Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.

Abstract Objective Defects in RARS2 cause cerebellopontine hypoplasia type 6 (pontocerebellar hypoplasia type 6, PCH6, OMIM: #611523), a rare autosomal recessive inherited mitochondrial disease. Here, we report two male patients and their respective family histories. Methods We describe the clinical presentation and magnetic resonance imaging (MRI) findings of these patients. Whole‐exome sequencing was used to identify the genetic mutations. Results One patient showed hypoglycemia, high lactic acid levels (fluctuating from 6.7 to 14.1 mmol/L), and frequent seizures after birth, with progressive atrophy of the cerebrum, cerebellum, and pons. The other patient presented with early infantile developmental and epileptic encephalopathies (EIDEEs) with an initial developmental delay followed by infantile epileptic spasm syndrome (IESS) at 5 months old, with no imaging changes. Whole‐exome sequencing identified compound heterozygous RARS2 variants c.25A>G (p.I9V) with c.1261C>T (p.Q421*) and c.1A>G (p.M1V) with c.122A>G (p.D41G) in these two patients. Of these loci, c.1261C>T and c.122A>G have not been previously reported. Significance Our findings have expanded the RARS2 gene variant spectrum and present EIDEEs and IESS as phenotypes which deepened the association between PCH6 and RARS2. Plain Language Summary Defects in RARS2 cause cerebellopontine hypoplasia type 6, a rare autosomal recessive inherited mitochondrial disease. Two patients with RARS2 variants were reported in this article. One patient showed hypoglycemia, high lactic acid levels, and frequent seizures after birth, with progressive atrophy of the cerebrum, cerebellum, and Page 3 of 21 Epilepsia OpenFor Review Only pons. The other patient presented with an initial developmental delay followed by refractory epilepsy at 5 months old, with no imaging changes. Our findings deepened the association between PCH6 and RARS2.

目的 探讨术前癫痫发作史与抗癫痫药物(ASMs)用药史对脑胶质瘤患者术前认知功能、情绪障碍的影响.方法 回顾性分析2016年6月～2020年6月本院收治的96例脑胶质瘤患者的临床资料,根据患者癫痫发作和用药情况分为A组(存在癫痫发作史且有ASMs用药史,n=33)、B组(存在癫痫发作史但无ASMs用药史,n=21)和C组(无癫痫发作史且无ASMs用药史,n=42),另选择同期于本院接受体检的健康体检者35例为对照组.比较各组一般临床资料、认知功能、焦虑和抑郁情绪状态.结果 A组Rivermead行为记忆测验(RBMT)评分、倒数N项测验(N-back)任务准确率低于B组、C组和对照组(P<0.05);B组N-back任务准确率低于对照组(P<0.05).A组、B组的数字连线测验A、B完成时间长于C组、对照组(P<0.05),数字符号测验和言语流畅性测验评分低于C组、对照组(P<0.05).各组贝克抑郁量表(BDI-Ⅱ)、贝克焦虑量表(BAI)评分比较:A组＞B组＞C组＞对照组(P<0.05).结论 癫痫发作史和ASMs用药史可能会增加脑胶质瘤患者术前记忆功能、执行功能受损的风险,诱发情绪障碍.

Objective:To analyze the clinical characteristics and genetic basis of two children patients with CHARGE syndrome.Methods:The clinical features of the two patients were analyzed, and potential variants were detected by Trio whole exome sequencing (trio-WES) of the probands and their parents.Results:Child 1 has manifested cerebellar vermis dysplasia, enlargement of cerebral ventricles, whereas child 2 manifested with infantile spasm and congenital hip dysplasia. Both children were found to harbor de novo heterozygous variants of the CHD7 gene, namely c. 4015C>T (exon 17) and c. 5050G>A (exon 22). Based on the guidelines of the American College of Medical Genetics and Genomics, the two variants were rated as pathogenic variants, and the related disease was CHARGE syndrome. Furthermore, child 2 was also found to harbor a novel heterozygous c. 6161A>C (p.Gln2054Pro) missense variant of COL12A1 gene, which was rated as possibly pathogenic, and the associated disease was Bethlem myopathy type 2, which is partially matched with the patient’s clinical phenotype. Conclusion:The special clinical phenotypes shown by the two children harboring novel CHD7 variants have further expanded the phenotypic spectrum of CHARGE syndrome.

Congenital disorder of glycosylation (CDG) is a group of genetic metabolic diseases involving multiple organs. A case of CDG caused by SLC35A2 gene mutation was diagnosed. The clinical characteristics included spasms, developmental retardation and multiple malformations. Video-electroencephalogram showed dysrhythmia. A de novo heterozygous missense mutation of SLC35A2 gene was detected by whole exome sequencing: c.844G>A (p.Gly282Arg). It was predicted to be likely pathogenic according to American College of Medical Genetics and Genomics guidelines which had not been reported in China.

BACKGROUND AND OBJECTIVE:Asparagine synthetase deficiency (ASNSD) is a rare neurometabolic disease caused by variations of the ASNS gene. It manifests as microcephaly, severe developmental delay, and spastic quadriplegia. 71% of ASNSD patients died during early infancy. We aim to investigate mutations related to intractable epilepsy in one Chinese genealogy.MATERIAL AND METHODS:Head Magnetic Resonance Imaging (MRI), whole exome sequencing (WES), and Liquid Chromatography-Mass Spectrometry (LC-MS) to help 2 patients with intractable epilepsy find the underlying mechanisms of disease.RESULTS:These two patients had a compound heterozygous mutation (c.224A > G, p.N75S and c.1612A > G, p.M538V) in the ASNS gene, of which c.1612A > G was a novel mutation. The asparagine levels in patients' plasmas were normal. In addition, they had a later onset, longer survival, and were milder than previously reported ASNSD patients.CONCLUSIONS:Two patients were diagnosed with a milder form of ASNSD. Clinically, the asparagine level in the patient's plasma cannot be used as the only basis to diagnose this disease. This study has expanded the disease phenotype spectrum of ASNSD and broadened the variation profile of the ASNS gene, which can assist in the clinical diagnosis and treatment of ASNSD patients.

Objective: The study aimed to identify the signatures of brain networks using electroencephalogram (EEG) in patients with infantile spasms (IS). Methods Scalp EEGs of subjects with IS were prospectively collected in the first year of life (n = 8; age range 4–8 months; 3 males, 5 females). Ten minutes of ictal and interictal EEGs were clipped and filtered into different EEG frequency bands. The values of each pair of EEG channels were directly compared between ictal with interictal onsets and the sleep-wake phase to calculate IS brain network attributes: characteristic path length (CPL), node degree (ND), clustering coefficient (CC), and betweenness centrality (BC). Results CPL, ND, and CC of the fast waves decreased while BC increased. CPL and BC of the slow waves decreased, while ND and CC increased during the IS ictal onset (P < 0.05). CPL of the alpha decreased, and BC increased during the waking time (P < 0.05). Conclusion The transmission capability of the fast waves, the local connectivity, and the defense capability of the slow waves during the IS ictal onset were enhanced. The alpha band played the most important role in both the global and local networks during the waking time. These may represent the brain network signatures of IS.

目的 探讨标准前颞叶切除术(SATL)联合选择性杏仁核、海马切除术(SelAH)对低级别胶质瘤(LGG)合并癫痫患者预后的影响.方法 选取2016年7月至2020年7月在郑州大学第三附属医院诊治的93例LGG合并癫痫患者,根据不同手术方式分为观察组(48例)和对照组(45例),观察组为SATL联合SelAH,对照组为SATL.比较两组术后早期癫痫发作情况,近远期并发症,日常生活能力(ADL)评分及术后12个月Engel分级的差异.结果 观察组近期并发症发生率为29.17％,与对照组的42.22％比较差异无统计学意义(P>0.05),但观察组早期癫痫发作发生率为8.33％,明显低于对照组的28.89％,差异有统计学意义(P<0.05);观察组远期并发症发生率为12.50％,与对照组的17.78％比较差异无统计学意义(P>0.05);术后6个月、12个月,观察组ADL评分分别为(70.02±4.33)分、(88.15±9.12)分,明显高于对照组的(60.47±3.69)分、(70.27±8.14)分,差异均有统计学意义(P<0.05);观察组术后12个月Engel分级情况优于对照组,且Ⅰ级例数占比75.00％,明显高于对照组的53.33％,差异有统计学意义(P<0.05).结论 SATL联合SelAH可有效控制早期、远期癫痫发作,且不会增加更多术后近、远期并发症,改善患者预后.

Objective:To explore the clinical and genetic characteristics of a case of early-onset epileptic encephalopathy caused by the UBA5 gene mutation and to review relevant literatures. Methods:The clinical characte-ristics and genetic data of a child with the UBA5 gene mutation in the Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University in June 2020 were retrospectively analyzed.Clinical characteristics and gene variation characteristics of the disease were reviewed in the domestic and foreign databases. Results:(1) The female patient presented infantile spasms at the age of 4 months.Electroencephalogram(EEG) suggested hypsarrhythmia and she was not responsive to a variety of anti-epileptic drugs.Besides, the patient showed severe cognitive and motor development delay, hypotonia, and microcephaly.The results of whole exome sequencing showed that the compound heterozygous mutation of UBA5 gene: exon 3 c. 214C>T (p.R72C) and exon 9 c. 844_c.845 insA (p.Y282Xfs*1), her father carries c. 214C>T mutation and her mother carries c. 844_c.845 INSA mutation.(2) To December 2020, a total of 15 cases of early-onset epileptic encephalopathy caused by the UBA5 gene mutation have been reported abroad.The main clinical manifestations were uncontrollable spasms, abnormal EEG findings, hypotonia, severe cognitive and movement disorders, microcephaly, and brain atrophy.A total of 11 mutation sites of the UBA5 gene were found, all belonging to the autosomal recessive inheritance, of which c. 1111G>A was the most common. Conclusions:The UBA5 gene mutation can lead to early-onset epileptic encephalopathy, which belongs to the autosomal recessive inheritance.It is featured by the early onset, uncontrollable seizures and poor long-term prognosis.

Objective:To summarize the clinical characteristics of drug-resistant epilepsy (DRE) in children and to analyze the efficacy of lamotrigine (LTG) add-on therapy for DRE in children of different seizure type, syndrome and etiological category.Methods:All cases of DRE patients treated with LTG or other antiseizure medication (ASM) adjunctive therapy in the Third Affiliated Hospital of Zhengzhou University from May 2019 to April 2020 were collected.The LTG add-on therapy group was treated with LTG add-on therapy, and the control group was treated with other ASM add-on therapy.The therapeutic effects of the two groups were compared.Results:A total of 134 cases meeting the requirement of research were collected, including 98 cases in the LTG add-on therapy group and 36 cases in the control group.For seizure of focal onset and unknown origin, there was statistical difference in efficacy between the LTG add-on therapy group and the control group ( Z=-2.48、-2.11, P<0.05), but for generalized DRE in children, there was no statistical difference in efficacy between the two groups ( Z=-0.39, P>0.05). There was a significantly statistical difference in curative effect between the LTG add-on therapy group and the control group for childhood DRE which could not be classified as any epileptic syndrome ( Z=-3.99, P<0.01), but there was no statistical difference in efficacy between the two groups for West syndrome and benign epilepsy accompanied by central temporal spikes ( Z=-0.94、-1.22, P>0.05). For childhood intractable epilepsy with unknown etiology, there was statistical difference in efficacy between the LTG add-on therapy group and the control group ( Z=-1.96, P<0.05), and for childhood intractable epilepsy with structural etiology, there was significantly statistical difference in efficacy between the two groups ( Z=-3.07, P<0.01), but there was no statistical difference in the efficacy for childhood intractable epilepsy with genetic etiology between the two groups ( Z=-1.02, P>0.05). Conclusion:The efficacy of LTG add-on therapy is significantly better than others for childhood DRE with seizure of focal onset or unknown origin, childhood DRE unclassified to any syndrome, and childhood DRE with structural etiology and unknown origin, especially with structural etiology.

目的 观察清醒期、睡眠期婴儿痉挛症(infantile spasms,IS)患儿痉挛发作期间不同频段脑功能网络属性特征路径长度(characteristic path length,CPL)的变化,探讨激素冲击治疗对IS患儿脑功能网络的作用.方法 IS患儿19例(IS组),均行甲泼尼龙或促肾上腺皮质激素冲击治疗;记录IS组激素冲击治疗前、后清醒期、睡眠期、清醒发作期、睡眠发作期脑电图数据,应用matlab软件分析delta、theta、alpha、beta、gamma频段CPL.选取同期行视频脑电图检查结果正常的儿童10例为对照组,比较2组清醒期、睡眠期脑电图delta、theta、alpha、beta、gamma频段CPL.随访1年,观察IS患儿激素冲击治疗后痉挛发作的控制情况.结果 随访1年,痉挛发作完全控制11例,治疗无效8例.激素冲击治疗前IS组患儿清醒期脑电图delta频段CPL[130.79(121.61,144.74)×10-3]高于对照组[128.50(119.11,140.78)×10-3](Z=-2.645,P=0.008),beta、gamma 频段 CPL[89.72(78.65,65 535.00)×10-3、94.22(83.98,65 535.00)×10-3]均低于对照组[107.87(90.37,65 535.00)×10-3、98.33(88.53,65 535.00)×10-3](Z=-9.236,P＜0.001;Z=-3.282,P=0.001);睡眠期脑电图 delta、beta 频段 CPL[129.17(118.06,140.99)×10-3、82.80(74.14,113.68)×10-3]均低于对照组[131.90(122.48,141.69)×10-3、92.38(76.94,65 535.00)×10-3](Z=-2.688,P=0.007;Z=-5.079,P＜0.001).清醒期IS组患儿激素冲击治疗后脑电图beta、gamma频段CPL[94.37(83.64,65 535.00)×10-3、97.98(88.04,65 535.00)×10-3]均高于激素冲击治疗前(Z=-4.503,P＜0.001;Z=-3.611,P＜0.001);睡眠期IS组患儿激素冲击治疗后脑电图beta频段CPL[89.65(79.43,65 535.00)×10-3]高于激素冲击治疗前(Z=-7.311,P＜0.001).IS患儿激素冲击治疗后清醒发作期脑电图delta、alpha、beta、gamma频段CPL[111.73(106.44,117.92)×10-3、110.75(103.97,130.07)×10-3、81.35(74.07,97.43)×10-3、92.61(79.01,65 535.00)×10-3]均低于冲击治疗前[118.16(110.58,130.23)×10-3、115.19(104.83,162.77)×10-3、90.53(76.98,65 535.00)×10-3、96.17(82.78,65 535.00)×10-3](P＜0.05);睡眠发作期脑电图 delta 频段 CPL[116.50(109.31,128.12)×10-3]高于冲击治疗前[113.66(107.56,121.60)×10-3](Z=-4.412,P＜0.001),theta 频段 CPL[131.56(114.90,177.63)×10-3]低于冲击治疗前[153.11(127.55,65 535.00)×10-3](Z=-6.109,P＜0.001).结论 IS患儿清醒期、睡眠期脑电图beta频段传输效率增强,激素冲击治疗可降低发作间期beta频段、睡眠发作期delta频段的传输效率,增强清醒发作期delta、alpha、beta、gamma频段的传输效率,改善脑电图高峰失律、减少高频振荡募集可能.